1. Field of the Invention
This invention relates to an improved method for the production of 2-(4'-isobutylphenyl)propionic acid, more commonly known as ibuprofen.
2. Description of Related Art
The following information is disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
Ibuprofen is a well-known nonsteroidal anti-inflammatory drug which has been converted from ethical, i.e., prescription, to over-the-counter status.
Japanese Kokai Patent No. SHO 55 [1980]-27,147, published Feb. 27, 1980 and assigned to Mitsubishi Petrochemical Co., discloses the formation of aryl substituted carboxylic acids, e.g., .alpha.-(4'-isobutylphenyl)propionic acid or ibuprofen, by reacting an aryl-substituted alcohol, e.g., 1-(4-isobutylphenyl)ethanol, with carbon monoxide and water in the presence of a hydrogen fluoride catalyst.
Japanese Kokai Patent No. SHO 59 [1984]-95,238, published Jun. 1, 1984 and assigned to Mitsubishi Petrochemical Co., teaches the formation of phenylacetic acid derivatives such as .alpha.-aryl-substituted propionic acids, where the aryl group may be a phenyl group containing at least one alkoxy, aryloxy, hydroxy, or amino group as an electron-donor substituent, by reacting a benzyl alcohol derivative, which may be an .alpha.-aryl substituted ethanol wherein the aryl group is the same as in the phenylacetic acid derivative product, with carbon monoxide and water, alcohol, or phenol, in the presence of a palladium catalyst. An acidic compound such as hydrogen chloride may be added as an auxiliary catalyst and a solvent such as benzene may also be used. The disclosure includes a comparative example in which ibuprofen (not included within the invention) is obtained in very low yield, i.e., 17.1%, when made utilizing the described process.
Japanese Kokai Patent No. SHO 59 [1984]-95,239, published Jun. 1, 1984 and assigned to Mitsubishi Petrochemical Co., discloses the formation of .alpha.-(6-methoxy-2-naphthyl)propionic acid by reacting .alpha.-(6-methoxy-2-naphthyl)ethyl alcohol with carbon monoxide and water in the presence of a palladium catalyst and an acidic compound, e.g., hydrogen chloride. The patent publication also states that if a non-halogen-containing acidic compound is used, it is desirable to add an ionizable metal halide to the reaction.
Japanese Kokuku Patent No. SHO 56 [1981]-35,659, published Sep. 4, 1978 and assigned to Ferrel International Societe Annonim, discloses an anhydrous method of producing a 2-(4'-isobutylphenyl)propionic acid ester by treating 1-(4'-isobutylphenyl)ethanol (IBPE) with carbon monoxide in a solution containing an alkanol and a catalyst such as palladium bis(triphenylphosphine) dichloro complex. The solution may also contain up to 10% of a mineral acid such as hydrogen chloride.
Pending application Ser. No. 07/357,381, filed May 24, 1989 by V. Elango et al., discloses a method for the preparation of ibuprofen by carbonylating 1-(4'-isobutylphenyl)ethanol (IBPE) with carbon monoxide under certain specific conditions utilizing a palladium catalyst in an aqueous acid medium. The entire disclosure of this application is hereby incorporated by reference.